ethyl 3-<4-<7-carbomethoxy-9-oxo-3-<3-<5-benzyloxy)-2-ethyl-4-phenylphenoxy>propoxy>-9H-xanthene>>propanoate | 171880-19-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: ethyl 3-<4-<7-carbomethoxy-9-oxo-3-<3-<5-benzyloxy)-2-ethyl-4-phenylphenoxy>propoxy>-9H-xanthene>>propanoate
• 英文别名: Methyl 5-(3-ethoxy-3-oxopropyl)-6-[3-(2-ethyl-4-phenyl-5-phenylmethoxyphenoxy)propoxy]-9-oxoxanthene-2-carboxylate
• CAS: 171880-19-6
• 化学式: C₄₄H₄₂O₉
• 分子量: 714.812
• InChiKey: IJYGLDYNAVMBFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.1
• 重原子数：
  53
• 可旋转键数：
  18
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  107
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ethyl 3-<4-<7-carbomethoxy-9-oxo-3-<3-<5-benzyloxy)-2-ethyl-4-phenylphenoxy>propoxy>-9H-xanthene>>propanoate 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 生成 5-(2-Ethoxycarbonyl-ethyl)-6-[3-(5-ethyl-2-hydroxy-biphenyl-4-yloxy)-propoxy]-9-oxo-9H-xanthene-2-carboxylic acid methyl ester
  参考文献：
  名称：

  联苯基取代的氧杂蒽酮：高效白三烯B4受体拮抗剂。

  摘要：

  DOI：

  10.1021/jm00076a030
• 作为产物：
  描述：

  1-bromo-2-(phenylmethoxy)-4-[(3-chloropropyl)oxy]-5-ethylbenzene 在 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 、 二甲基亚砜 、 potassium iodide 作用下， 以 乙醇 、 丁酮 、 苯 为溶剂， 反应 34.0h， 生成 ethyl 3-<4-<7-carbomethoxy-9-oxo-3-<3-<5-benzyloxy)-2-ethyl-4-phenylphenoxy>propoxy>-9H-xanthene>>propanoate
  参考文献：
  名称：

  Synthetic and Structure/Activity Studies on Acid-Substituted 2-Arylphenols: Discovery of 2-[2-Propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]- propoxy]phenoxy]benzoic Acid, a High-Affinity Leukotriene B4 Receptor Antagonist

  摘要：

  Structural derivatives of LY255283 have been studied as receptor antagonists of leukotriene B-4. Substitution of the 2-hydroxyacetophenone subunit of 1 (LY255283) with a 2-arylphenol group provided entry into several new series that feature various mono- and diacidic core functionality. These new analogues, the subject of a broad structure-activity investigation, displayed significantly increased in vitro and in vivo activity as receptor antagonists of LTB(4). A series of diaryl ether carboxylic acids demonstrated especially interesting activity and led to the discovery of compound 43b, 2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]- propoxy]phenoxy]benzoic acid (LY293111), a 2-arylphenol-substituted diaryl ether carboxylic acid which displayed potent binding to human neutrophils (IC50 = 17 +/- 14.6 nM) and guinea pig lung membranes (IC50 6.6 +/- 0.71 nM), inhibition of LTB(4)-induced expression of the CD11b/CD18 receptor on human neutrophils (IC50 - 3.3 +/- 0.81 nM), and inhibition of LTB(4)-induced contraction of guinea pig lung parenchyma (pK(B) = 8.7 +/- 0.16). In vivo, 43b demonstrated potent activity in inhibiting LTB(4)-induced airway obstruction in the guinea pig when dosed by the oral (ED(50) = 0.40 mg/kg) or intravenous (ED(50) = 0.014 mg/kg) routes. A specific LTB(4) receptor antagonist, 43b had little effect on inhibiting contractions of guinea pig lung parenchyma induced by leukotriene D-4 (LTD(4)), histamine, carbachol, or U46619. Compound 43b has been chosen as a clinical candidate and is currently in phase I studies for a variety of inflammatory diseases.

  DOI：

  10.1021/jm00022a006

文献信息

• Biphenylyl-substituted xanthones: highly potent leukotriene B4 receptor antagonists
  作者：J. Scott Sawyer、Ronald F. Baldwin、Michael J. Sofia、Paul Floreancig、Philip Marder、David L. Saussy、Larry L. Froelich、Steven A. Silbaugh、Peter W. Stengel

  DOI：10.1021/jm00076a030

  日期：1993.11
• Synthetic and Structure/Activity Studies on Acid-Substituted 2-Arylphenols: Discovery of 2-[2-Propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]- propoxy]phenoxy]benzoic Acid, a High-Affinity Leukotriene B4 Receptor Antagonist
  作者：J. Scott Sawyer、Nicholas J. Bach、S. Richard Baker、Ronald F. Baldwin、Peter S. Borromeo、Sandra L. Cockerham、Jerome H. Fleisch、Paul Floreancig、Larry L. Froelich

  DOI：10.1021/jm00022a006

  日期：1995.10

  Structural derivatives of LY255283 have been studied as receptor antagonists of leukotriene B-4. Substitution of the 2-hydroxyacetophenone subunit of 1 (LY255283) with a 2-arylphenol group provided entry into several new series that feature various mono- and diacidic core functionality. These new analogues, the subject of a broad structure-activity investigation, displayed significantly increased in vitro and in vivo activity as receptor antagonists of LTB(4). A series of diaryl ether carboxylic acids demonstrated especially interesting activity and led to the discovery of compound 43b, 2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]- propoxy]phenoxy]benzoic acid (LY293111), a 2-arylphenol-substituted diaryl ether carboxylic acid which displayed potent binding to human neutrophils (IC50 = 17 +/- 14.6 nM) and guinea pig lung membranes (IC50 6.6 +/- 0.71 nM), inhibition of LTB(4)-induced expression of the CD11b/CD18 receptor on human neutrophils (IC50 - 3.3 +/- 0.81 nM), and inhibition of LTB(4)-induced contraction of guinea pig lung parenchyma (pK(B) = 8.7 +/- 0.16). In vivo, 43b demonstrated potent activity in inhibiting LTB(4)-induced airway obstruction in the guinea pig when dosed by the oral (ED(50) = 0.40 mg/kg) or intravenous (ED(50) = 0.014 mg/kg) routes. A specific LTB(4) receptor antagonist, 43b had little effect on inhibiting contractions of guinea pig lung parenchyma induced by leukotriene D-4 (LTD(4)), histamine, carbachol, or U46619. Compound 43b has been chosen as a clinical candidate and is currently in phase I studies for a variety of inflammatory diseases.